Affiliations 

  • 1 Department of Pharmacy, Sarhad University of Science & Information Technology, Peshawar
  • 2 Department of Pharmacy, University of Malakand, Chakdara, Pakistan
  • 3 Department of Pharmacy, University of Malakand, Chakdara, Pakistan; Institute of Life Sciences Research, School of Pharmacy, University of Bradford, West Yorkshire
  • 4 Department of Pharmacy, University of Swabi, KPK, Pakistan
  • 5 SEDA Pharmaceutical Development Services, The BioHub at Alderley Park, Cheshire, UK
  • 6 Faculty of Pharmacy, Department of Pharmaceutics, Universiti Teknologi MARA, Selangor, Malaysia
  • 7 Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur Pakistan, Bahawalpur, Pakistan
  • 8 Riyadh Community College, King Saud University, Riyadh, Saudi Arabia
  • 9 Institute of Life Sciences Research, School of Pharmacy, University of Bradford, West Yorkshire
Drug Des Devel Ther, 2016;10:3837-3850.
PMID: 27920499

Abstract

Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena(®) DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C-8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena(®) DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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